A serum-resistant polyamidoamine-based polypeptide dendrimer for gene transfection

作者：Wu, H M^*; Pan, S R; Chen, M W; Wu, Y; Wang, C; Wen, Y T; Zeng, X; Wu, C B

来源：Biomaterials, 2011, 32(6): 1619-1634.

DOI：10.1016/j.biomaterials.2010.09.045

• Polyamidoamine
• Poly amino acid
• Polycation
• Serum-resistant
• Gene transfer
• Surface modification

A serum tolerant polycation gene vector, G(2) PAMAM-PGlu-G(1) PAMAMs (ALA), was designed, synthesized, characterized and evaluated. A honeycomb-like molecular structure model for mechanistic explanation of ALA was postulated and discussed. Designed as a star-shaped polyamidoamine (PAMAM)-based polypeptide dendrimer through peptide bond linkages, ALA was with non-toxic low generation G(2) PAMAM (G(2)) as its central core, polyglutamate (PGlu)s as its star-shaped backbone branches and G(1) PAMAM (G(1))s as its branch grafts and peripheral terminals. IR, (1)H NMR demonstrated its successful combination. As a gene carrier, ALA exhibited good DNA binding and condensation capacity with particle size (similar to 87 nm for N/P 40, similar to 170 nm for N/P 30) and zeta-potential (similar to 16 mV for N/P 30-40), negligible cytotoxicity, exciting serum tolerant capacity and significant serum-promoted (serum-containing 56.6%> serum-free 32.7%), cell line dependent (Hek 293 > Bel 7402 > Hela), incubation period dependent (38 h > 18 h > 12 h > 9 h > 4 h > 2 h > 1 h) and sustained (peak transfection appeared at 30 h incubation) transfection efficiency. The presence of serum had not only no inhibition on, but also prominent promotion to, the transfection activity of ALA. All above features differentiated ALA clearly from most other serum-inhibitive nonviral gene carriers, and proved ALA the promising and challenging potential efficient gene vector for practical clinical application.

• 出版日期2011-2
• 单位中山大学